Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94±15.5% vs. 17.1±3.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.     

Nutritional Value-Dependent and Nutritional Value-Independent Effects on Drosophila melanogaster Larval Behavior

Gustatory stimuli allow an organism not only to orient in its environment toward energy-rich food sources to maintain nutrition but also to avoid unpleasant or even poisonous substrates. For both mammals and insects, sugars-perceived as "sweet"-potentially predict nutritional benefit. Interestingly, even Drosophila adult flies are attracted to most high-potency sweeteners preferred by humans. However, the gustatory information of a sugar may be misleading as some sugars, although perceived as "sweet," cannot be metabolized. Accordingly, in adult Drosophila, a postingestive system that additionally evaluates the nutritional benefit of an ingested sugar has been shown to exist. By using a set of seven different sugars, which either offer (fructose, sucrose, glucose, maltodextrin, and sorbitol) or lack (xylose and arabinose) nutritional benefit, we show that Drosophila, at the larval stage, can perceive and evaluate sugars based on both nutrition-dependent and -independent qualities. In detail, we find that larval survival and feeding mainly depend on the nutritional value of a particular sugar. In contrast, larval choice behavior and learning are regulated in a more complex way by nutrition value-dependent and nutrition value-independent information. The simplicity of the larval neuronal circuits and their accessibility to genetic manipulation may ultimately allow one to identify the neuronal and molecular basis of the larval sugar perception systems described here behaviorally.     

Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome

Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several preclinical and clinical observations suggest that Treg can be depleted by cyclophosphamide. Over a period of 3?months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50?mg cyclophosphamide p.o. daily. Cyclophosphamide treatment initially caused a significant reduction in circulating Treg by more than 40% (P?=?0.002). However, Treg numbers completely recovered during the treatment due to increased proliferative activity and maintained their suppressive capacity. Treg depletion coincided with a strong increase in breast tumor-reactive T cells (P?=?0.03) that remained at high levels during the whole period. Numbers of tumor-reactive T cells but not of Treg correlated with disease stabilization (P?=?0.03) and overall survival (P?=?0.027). We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients.     

Improving Product Specificity of Whole‐Cell Alkane Oxidation in Nonconventional Media: A Multivariate Analysis Approach

Two‐liquid‐phase reaction media have long been used in bioconversions to supply or remove hydrophobic organic reaction substrates and products to reduce inhibitory and toxic effects on biocatalysts. In case of the terminal oxyfunctionalization of linear alkanes by the AlkBGT monooxygenase the excess alkane substrate is often used as a second phase to extract the alcohol, aldehyde, and acid products. However, the selection of other carrier phases or surfactants is complex due to a large number of parameters that are involved, such as biocompatibility, substrate bioavailability, and product extraction selectivity. This study combines systematic high‐throughput screening with chemometrics to correlate physicochemical parameters of a range of cosolvents to product specificity and yield using a multivariate regression model. Partial least‐squares regression shows that the defining factor for product specificity is the solubility properties of the reaction substrate and product in the cosolvent, as measured by Hansen solubility parameters. Thus the polarity of cosolvents determines the accumulation of either alcohol or acid products. Whereas usually the acid product accumulates during the reaction, by choosing a more polar cosolvent the 1‐alcohol product can be accumulated. Especially with Tergitol as a cosolvent, a 3.2‐fold improvement in the 1‐octanol yield to 18.3 mmol L^?1 is achieved relative to the control reaction without cosolvents.     

The significance of carnivory for the fitness of Drosera in its natural habitat

Summary The effects on Drosera intermedia and D. rotundifolia of supplementary feeding with Drosophila melanogaster were studied in plants growing in their natural habitat. The artificial food supply was within the natural range of prey quantity. In both species supplementary feeding led to significantly higher dry weights of summer and winter plant, more leaves, more flowers, more seeds, and a larger trapping area. The dry weight of plants increased much more than the dry weight of prey added, indicating a fertilizing effect. Thus, animal food supply is an important limiting factor in the field. The essential component of the prey is probably its mineral content. There were significant differences between the two species of sundew. In D. rotundifolia the effect of feeding on dry weight was smaller and plants nerver showed axillary budding. However the effect on the percentage of blooming plants was more than twice as strong as in D. intermedia. Considering only the prey actually absorbed per unit of plant biomass, both species show about the same fertilizing effect. The number of fruits per unit of biomass was about twice as large in D. rotundifolia as in D. intermedia. The reasons for these differences are discussed in the light of niche segregation with respect to habitat and range of prey.     

The significance of carnivory for the fitness of Drosera in its natural habitat

Summary A field study of two carnivorous plant species, Drosera intermedia and D. rotundifolia, was carried out in a small silting-up bog in Southern Bavaria (FR Germany). Various parameters of undisturbed individuals of both species were measured for a period of two years and subjected to a partial correlation analysis. The importance of prey as a limiting factor for various fitness parameters was confirmed for both species. Other factors may occasionally also be limiting, e.g. assimilation area and water supply. Benefits obtained from the prey are partly transferred to the next year via the winter bud. The importance of the relative demonstrated: Plants of D. rotundifolia showed higher fitness values in higher positions, those of D. intermedia in lower positions. Growth characteristics of both species tended to influence the height of their own position in a corresponding direction: D. intermedia downwards and D. rotundifolia upwards. In both species negative effects of intraspecific neighbourhood were evident, whereas interspecific effects were not detectable. Plants of D. intermedia tend to influence their neighbourhood situation by changing their position by rhizome-like stem growth. In D. intermedia the decision to reproduce by seeds or axillary buds seems to be made at least partially already in the year before. D. rotundifolia was only observed reproducing by seeds. In spite of different catching characteristics (plant shape, plant size, microhabitats, prey spectra), the general catching success, measured as prey biomass per plant biomass, was equal in both species of sundew. This agrees with earlier findings that in this bog both species have the same biomass per ground area.     

The significance of opportunistic predators for the sympatric carnivorous plant species Drosera intermedia and Drosera rotundifolia

Summary Earlier feeding experiments with Drosera in the field using adult Drosophila melanogaster as prey had shown that D. intermedia reacts three times as strong with respect to biomass production as the sympatric species D. rotundifolia. The present study shows that in D. rotundifolia only 29% of added flies remain on the leaves for more than 24 h, but 95% in D. intermedia. Opportunistic predators, mostly ants, are likely to be responsible for this difference. Ants were often observed robbing food from the leaves of D. rotundifolia, and showed a much higher activity in the microhabitat of this species. In both species of Drosera larger individuals were better than smaller ones in retaining added flies. The activity of ants significantly increased with air temperature and the duration of sunshine. The advantage of plundering seems to be more important for the ants than the danger of being caught. The prey collected from Drosera may be an important source of food for bog-dwelling ants.